This invention relates generally to liquid transfer and dispensing devices for liquid reagents and samples, and more particularly to an automated apparatus and method for handling magazines containing pipetting tips.
Pipetting systems are well known, and typically are used in laboratories and hospitals for the aspiration and dispensing of relatively small, predetermined quantities of liquids into the wells of plates such as microplates, deep-well blocks and the like. Examples of liquids being dispensed include blood, other biological samples, solvents, reagents, and the like. Some or all of the liquid is normally drawn by suction through pipette tips from one set of plates or a reservoir of liquid and is subsequently released through the pipette tips into the wells of other plates.
Not all plates have the same well spacings, and not all plates have the same number of wells. Therefore, it is desirable to vary the number of pipette tips, or the spacings between tips in such automated systems to accommodate plates with different well numbers and spacings. Moreover, it is desirable to be able to replace used pipette tips with unused ones. Such flexibility is essential in most laboratories and hospitals. It is also desirable to be able to perform such operations rapidly, and to be able to perform a high volume of operations in a very short period of time.
In existing high volume, automated, multichannel pipetting systems, typically trays or magazines of disposable pipette tips are positioned in the dispensing head of the pipettor. Such magazines are configured to support a predetermined number of tips of a certain size and with a defined spacing. Each pipette tip has an enlarged upper end which is configured to be engaged in sealing relation to with an apparatus for aspirating liquid into the tip and expelling it therefrom. The lower end of each tip is tapered and has an opening through which liquid in a well of a microplate or a supply reservoir is withdrawn and expelled. Typically, these magazines are removable from the dispensing head of the pipetting apparatus to allow replacement of one magazine of pipette tips with another to prevent contamination of liquid from one pipetting operation with that of another pipetting operation. These tips may either be disposed of or washed for future pipetting operations. In some existing, automated pipetting apparatus, the magazines containing tips are manually replaced, while in others, the insertion and removal of magazines is accomplished in an automatic or semi-automatic fashion. These exchanges should be performed rapidly and automatically to maintain a high throughput, and to minimize needed operator time. Automated systems performing such exchanges must be able to interface with existing automated pipetting systems.
An example of an automated pipetting system which uses magazines containing pipette tips is disclosed in co-pending U.S. application Ser. No. 09/865,404, filed May 25, 2001, and assigned to the Assignee of the present application. Other automated, high volume systems include those shown in U.S. Pat. Nos. 4,830,832; 6,148,878; and 5,988,236. An example of an existing automated pipette tip changer is sold by Cybio AG of Jena, Germany.
The present invention relates to a method and apparatus for handling magazines containing pipette tips and is used in conjunction with high volume, automated pipetting systems. In particular, the present invention is used with automated pipetting systems which have a dispensing head configured to receive a magazine of pipette tips in which one magazine of used or inappropriately sized tips can be replaced with another magazine of unused or appropriately sized tips.
One aspect of the invention relates to a magazine handling apparatus having one or more gripper heads for gripping a magazine. These gripper heads are associated with a transfer apparatus which moves the gripper heads from a dispensing head of a pipettor to a location for disposal of used magazines containing pipette tips, and from a source of unused magazines containing unused pipette tips to the dispensing head of the automated pipettor. In one embodiment of this aspect, two gripper heads are disclosed, and one gripper head is configured to grip only a used magazine with used pipette tips and convey the used magazine from the pipettor to a disposal location. The other gripper head is configured to grip only an unused magazine with unused tips and convey the unused magazine from a source of unused magazines to the dispensing head of the pipettor. In another embodiment of this invention, the two gripper heads are disposed vertically, one above the other, with the upper gripper head being the gripper configured only to grip unused magazines, while the lower gripper head is configured to only grip used magazines with used pipette tips.
In another embodiment of this aspect of the invention, each gripper head includes a sensor which senses a particular location on a tip magazine to align the gripper head with the magazine. In particular, in a preferred embodiment, the location sensed is a tab or handle on the magazine which is to be grasped by the gripper head. Preferably, the sensor is a converging, diffuse, reflective sensor which has a controlled depth of field.
In another aspect of the invention, the source of unused tips and magazines is a carousel accessible by a gripper head. In one embodiment, the carousel includes a plurality of stacker assemblies each of which is configured to contain a plurality of magazines and associated pipette tips. Each stacker assembly is removable from the carousel for filling thereof with magazines and tips, and each stacker assembly is replaceable into the carousel when filled with magazines and tips. Each stacker assembly has an open side which may be aligned with an opening in the carousel which is accessible by a gripper head. In another embodiment, the carousel is automatically rotated until a source of unused magazines and tips is disposed adjacent the opening accessible by the gripper head. In yet another embodiment of this aspect, the carousel is disposed vertically below the dispensing head on the automated pipetting system.
In another aspect of the invention, a method is provided for automatically removing used or dirty magazines and pipette tips from the dispensing head of an automated pipetting system, and replacing the used magazine with an unused magazine with unused tips. In one embodiment of this aspect, the method includes the steps of removing the used magazine from the dispensing head using an automated gripper, inserting an unused magazine in the dispensing head in place of the used magazine, and conveying the used magazine to a disposal location. In one embodiment of this method, two gripper heads are used, and one gripper head carries only unused magazines and the other gripper head carries only used magazines. In a further embodiment, the one gripper head carries an unused magazine ready for insertion into the dispensing head prior to the removal of the used magazine by the other gripper head, so that the unused magazine is inserted upon removal of the used magazine. Preferably, in this embodiment, the gripper head holding the unused magazine is disposed above the gripper head holding the used magazine, so that the unused magazine is not contaminated by the used magazine.
In a further embodiment of the method of this invention, clean, unused magazines are stored in a carousel in a stacked array. The gripper head searches for the next available magazine, retrieves it from an opening in the carousel, and returns to the dispensing head to await completion of the pipetting operation, and removal of the used magazine. In this embodiment of the method, the magazines may be stored in a stacker which can be retrieved from the carousel and replaced after being filled with new, unused magazines and tips. The carousel may be automatically rotated to a position such that a stacker containing unused magazines is presented to an opening which can be accessed by the gripper head. In another embodiment of the method, the carousel is disposed vertically below the dispensing head in the automated pipettor.
The foregoing method and apparatus permit rapid, accurate and automated replacement of pipette tip magazines in the dispensing head of an automated pipettor.